1: Lengsin is a novel member of the glutamine synthetase (GS) superfamily that is specific for the vertebrate eye lens. Lengsin is expressed specifically in the layer of terminally differentiating secondary fiber cells in which nuclei and other organelles are lost and cytoskeleton and intracellular junctions are reorganized. Y2H experiments suggest that lengsin has a role as a chaperone of major cytoskeletal components of the lens and participates in the reorganization of cellular components in terminal differentiation.A knock out model of lengsin has been produced which gives rise to age-related cortical cataract. Lengsin is also a candidate locus for ARCC1 in humans and is under evaluation. 3: Retbindin is a novel protein of the retina. We have shown that retbindin is essentially specific for photoreceptors and that the human gene has separate cone and rod cell promoters. A transgenic mouse model shows suggests that retbindin has a role in control of retinoid and carotenoid levels in the retina. 4: AMD and complement factor H (CFH). Common sequence variants of CFH have major roles in determining susceptibility to age-related macular degeneration (AMD). Using yeast 2-hybrid libraries for aged human RPE/choroid and retina and bait constructs for the AMD-related domain 7 of CFH we have identified potentially important targets for CFH binding in human RPE/choroid. These results have been confirmed by immunofluorescence localization and have implications for intervention in the progression of AMD. Work is in progress to develop an assay to investigate drugs that could modulate this binding activity.